Efeito do telmisartan na encefalopatia hepática experimental

Abstract

Type A hepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from acute liver failure. The origin of this condition is associated with the peripheral accumulation of ammonia and the triggering of neuroinflammation, originating both locally and peripherally. The classic and alternative pathways of the renin-angiotensin system (RAS) modulate inflammation and influence the immune response; however, an imbalance between these pathways has been demonstrated in different experimental models of cerebrovascular diseases. Recently, our research group detected an upregulation of angiotensin-converting enzyme (ACE) and a downregulation of angiotensin 1-7 (Ang 1-7), associated with increased inflammation in the central nervous system during an HE experiments. In this context, we used female C57BL/6 mice to investigate the effect of telmisartan, an antagonist of the angiotensin II (Ang-II) AT1 receptor, in a TAA-induced HE model. Mice (n=40) were randomly distributed into four distinct groups: TAA group, saline group; TAA+Telmi group; and Telmi group. The animals were treated with 10mg/kg of telmisartan or saline 6 hours after TAA or saline administration, and the treatment was maintained every 12 hours over a period of three days. We observed that TAA administration resulted in a reduction in the locomotor activity 24 hours after the induction of HE. However, treatment with telmisartan attenuated this effect. Moreover, while animals exposed to TAA showed extensive areas of hepatocellular necrosis, those treated with telmisartan did not reveal this parameter on the third day after the induction of HE by TAA, indicating potential hepatoprotection effect. In this context, we propose that treatment with telmisartan promoted improvement in locomotor deficits and hepatic lesions in mice exposed to a single administration of 600 mg/kg of TAA. Keywords: Acute hepatic encephalopathy; Telmisartan; Renin-Angiotensin System.